1ql6: Difference between revisions

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{{Seed}}
[[Image:1ql6.png|left|200px]]


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==THE CATALYTIC MECHANISM OF PHOSPHORYLASE KINASE PROBED BY MUTATIONAL STUDIES==
The line below this paragraph, containing "STRUCTURE_1ql6", creates the "Structure Box" on the page.
<StructureSection load='1ql6' size='340' side='right'caption='[[1ql6]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1ql6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QL6 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_1ql6|  PDB=1ql6  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ql6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ql6 OCA], [https://pdbe.org/1ql6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ql6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ql6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ql6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PHKG1_RABIT PHKG1_RABIT] Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3.<ref>PMID:8454596</ref> <ref>PMID:8999860</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ql/1ql6_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ql6 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The contributions to catalysis of the conserved catalytic aspartate (Asp149) in the phosphorylase kinase catalytic subunit (PhK; residues 1-298) have been studied by kinetic and crystallographic methods. Kinetic studies in solvents of different viscosity show that PhK, like cyclic AMP dependent protein kinase, exhibits a mechanism in which the chemical step of phosphoryl transfer is fast and the rate-limiting step is release of the products, ADP and phosphoprotein, and possibly viscosity-dependent conformational changes. Site-directed mutagenesis of Asp149 to Ala and Asn resulted in enzymes with a small increase in K(m) for glycogen phosphorylase b (GPb) and ATP substrates and dramatic decreases in k(cat) (1.3 x 10(4) for Asp149Ala and 4.7 x 10(3) for Asp149Asn mutants, respectively). Viscosometric kinetic measurements with the Asp149Asn mutant showed a reduction in the rate-limiting step for release of products by 4.5 x 10(3) and a significant decrease (possibly as great as 2.2 x 10(3)) in the rate constant characterizing the chemical step. The date combined with the crystallographic evidence for the ternary PhK-AMPPNP-peptide complex [Lowe et al. (1997) EMBO J. 6, 6646-6658] provide powerful support for the role of the carboxyl of Asp149 in binding and orientation of the substrate and in catalysis of phosphoryl transfer. The constitutively active subunit PhK has a glutamate (Glu182) residue in the activation segment, in place of a phosphorylatable serine, threonine, or tyrosine residue in other protein kinases that are activated by phosphorylation. Site-directed mutagenesis of Glu182 and other residues involved in a hydrogen bond network resulted in mutant proteins (Glu182Ser, Arg148Ala, and Tyr206Phe) with decreased catalytic efficiency (approximate average decrease in k(cat)/K(m) by 20-fold). The crystal structure of the mutant Glu182Ser at 2.6 A resolution showed a phosphate dianion about 2.6 A from the position previously occupied by the carboxylate of Glu182. There was no change in tertiary structure from the native protein, but the activation segment in the region C-terminal to residue 182 showed increased disorder, indicating that correct localization of the activation segment is necessary in order to recognize and present the protein substrate for catalysis.


===THE CATALYTIC MECHANISM OF PHOSPHORYLASE KINASE PROBED BY MUTATIONAL STUDIES===
Catalytic mechanism of phosphorylase kinase probed by mutational studies.,Skamnaki VT, Owen DJ, Noble ME, Lowe ED, Lowe G, Oikonomakos NG, Johnson LN Biochemistry. 1999 Nov 2;38(44):14718-30. PMID:10545198<ref>PMID:10545198</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1ql6" style="background-color:#fffaf0;"></div>
(as it appears on PubMed at http://www.pubmed.gov), where 10545198 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_10545198}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
1QL6 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QL6 OCA].
 
==Reference==
<ref group="xtra">PMID:10545198</ref><references group="xtra"/>
[[Category: Oryctolagus cuniculus]]
[[Category: Oryctolagus cuniculus]]
[[Category: Phosphorylase kinase]]
[[Category: Johnson LN]]
[[Category: Johnson, L N.]]
[[Category: Lowe ED]]
[[Category: Lowe, E D.]]
[[Category: Noble MEM]]
[[Category: Noble, M E.M.]]
[[Category: Oikonomakos NG]]
[[Category: Oikonomakos, N G.]]
[[Category: Owen DJ]]
[[Category: Owen, D J.]]
[[Category: Skamnaki VT]]
[[Category: Skamnaki, V T.]]
[[Category: Atp-binding]]
[[Category: Calmodulin-binding]]
[[Category: Glycogen metabolism]]
[[Category: Kinase]]
[[Category: Serine/threonine-protein]]
[[Category: Transferase]]
 
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